ArticleThe Journal of biological chemistry2015
Regulation of GATA-binding protein 2 levels via ubiquitin-dependent degradation by Fbw7: involvement of cyclin B-cyclin-dependent kinase 1-mediated phosphorylation of THR176 in GATA-binding protein 2.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Hypoxia-Induced O-GlcNAcylation of GATA3 Leads to Excessive Testosterone Production in Preeclamptic Placentas.MedComm · 2025Article
- Combinatorial mapping of E3 ubiquitin ligases to their target substrates.Molecular cell · 2025Article
- CDK1 inhibition reduces osteogenesis in endothelial cells in vascular calcification.JCI insight · 2024Article
- Linking GATA2 to myeloid dysplasia and complex cytogenetics in adult myelodysplastic neoplasm and acute myeloid leukemia.Blood advances · 2024Article
- Targeting CDK1 in cancer: mechanisms and implications.NPJ precision oncology · 2023Review
- E3 ubiquitin ligase on the biological properties of hematopoietic stem cell.Journal of molecular medicine (Berlin, Germany) · 2023Review
- A COP1-GATA2 axis suppresses AR signaling and prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Systematic Discovery of FBXW7-Binding Phosphodegrons Highlights Mitogen-Activated Protein Kinases as Important Regulators of Intracellular Protein Levels.International journal of molecular sciences · 2022Article
- Proteasome-Mediated Regulation of GATA2 Expression and Androgen Receptor Transcription in Benign Prostate Epithelial Cells.Biomedicines · 2022Article
- CDK1/FBXW7 facilitates degradation and ubiquitination of MLST8 to inhibit progression of renal cell carcinoma.Cancer science · 2022Article
- Impairment of the Hypothalamus-Pituitary-Thyroid Axis Caused by Naturally OccurringInternational journal of molecular sciences · 2021Article
- Human GATA2 mutations and hematologic disease: how many paths to pathogenesis?Blood advances · 2020Review
- Article
- Pseudopodium-enriched atypical kinase 1 mediates angiogenesis by modulating GATA2-dependent VEGFR2 transcription.Cell discovery · 2018Article
- PIASy antagonizes Ras-driven NSCLC survival by promoting GATA2 SUMOylation.Journal of Cancer · 2018Article
- G-Protein Dependent Signal Transduction and Ubiquitination in Dictyostelium.International journal of molecular sciences · 2017Review
- The critical role of SENP1-mediated GATA2 deSUMOylation in promoting endothelial activation in graft arteriosclerosis.Nature communications · 2017Article
- CDK5/FBW7-dependent ubiquitination and degradation of EZH2 inhibits pancreatic cancer cell migration and invasion.The Journal of biological chemistry · 2017Article
- The GATA factor revolution in hematology.Blood · 2017Review
- The emerging role of GATA transcription factors in development and disease.Expert reviews in molecular medicine · 2016Review
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A GATA family transcription factor, GATA-binding protein 2 (GATA2), participates in cell growth and differentiation of various cells, such as hematopoietic stem cells. Although its expression level is controlled by transcriptional induction and proteolytic degradation, the responsible E3 ligase has not been identified. Here, we demonstrate that F-box/WD repeat-containing protein 7 (Fbw7/Fbxw7), a component of Skp1, Cullin 1, F-box-containing complex (SCF)-type E3 ligase, is an E3 ligase for GATA2. GATA2 contains a cell division control protein 4 (Cdc4) phosphodegron (CPD), a consensus motif for ubiquitylation by Fbw7, which includes Thr(176). Ectopic expression of Fbw7 destabilized GATA2 and promoted its proteasomal degradation. Substitution of threonine 176 to alanine in GATA2 inhibited binding with Fbw7, and the ubiquitylation and degradation of GATA2 by Fbw7 was suppressed. The CPD kinase, which mediates the phosphorylation of Thr(176), was cyclin B-cyclin-dependent kinase 1 (CDK1). Moreover, depletion of endogenous Fbw7 stabilized endogenous GATA2 in K562 cells. Conditional Fbw7 depletion in mice increased GATA2 levels in hematopoietic stem cells and myeloid progenitors at the early stage. Increased GATA2 levels in Fbw7-conditional knock-out mice were correlated with a decrease in a c-Kit high expressing population of myeloid progenitor cells. Our results suggest that Fbw7 is a bona fide E3 ubiquitin ligase for GATA2 in vivo.
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